Preliminary prostate cancer screening data from the Afro- Caribbean population aged 50-79 on the Caribbean island of Tobago revealed a high rate (29 percent) of elevated PSA (greater than 4ng/ml). Of the 79 percent undergoing biopsy, 51 percent were diagnosed with prostate cancer. High incidence of prostate cancer has recently been reported among Afro-Caribbean Jamaicans. These data suggest that the elevated risk for prostate cancer, observed in African Americans, is present in other populations of West African descent. This strongly suggests that prostate cancer risk is influenced by genetic component(s) in combination with lifestyles/metabolic factors common across populations of African descent living in diverse environments. We propose to conduct a molecular epidemiology study of prostate cancer in the Tobago male population, aged 40-79 (n=5121), (92 percent of African descent). We are currently screening the population, aged 50-79 (n=3000) using serum (prostate specific antigen) PSA (greater than 4 ng/ml) and digital rectal exam (DRE). This proposed study will screen men aged 40-49 (n=1800) for elevated PSA (greater than 2ng/ml) or abnormal DRE, in addition to men aged 50-79. We expect to study 300 screening detected cases compared with 300 frequency age matched controls. We will determine whether variants in candidate genes related to sex hormone metabolism, growth factor, vitamin D, PSA transport and toxic substance metabolism, or to loci for familial prostate cancer of chromosomes 1 and X, are associated with prostate cancer, and whether gene frequencies differ from published studies of Caucasian and African American populations. Other molecular markers will include serum arachidonic acid and IGF-1 (for each, hypothesize high levels in cases). Bone mineral density, a surrogate for long term IGF-1 and sex hormone exposure, and central fat distribution will be measured (for each, hypothesize elevated in cases). This large, very cooperative, male population of West African descent, provides a unique opportunity for the study of prostate cancer risk because prostate cancer risk is high, the population is primarily of West African descent, and there is less admixture than among African Americans. Understanding the contribution of environment, genetic and metabolic factors will lead to measures to reduce the risk for prostate cancer among men of West African descent in the U.S., the Caribbean and other geographic areas.